The ubiquitin/proteasome pathway is a widely studied system, which is involved, in many cellular processes. Ubiquitin conjugates itself to other proteins targeting them for degradation or possibly activating other pathways. One process with which it interacts is the nucleotide excision repair pathway through the human homologue of rad 23 NB (HHR23NB) proteins. This relationship is not well understood and is in need further study. The aim of this proposal is to characterize the structure/function relationships between ubiquitin and HHR23A using multidimensional, multinuclear NMR techniques. The third participant in this system, which will be studied, is the HIV-1 vpr protein, which interacts with a C-terminal domain of HHR23A to induce cell cycle arrest. The complex relationship between these proteins as they relate to DNA repair, ubiquitination, and HIV infection will be investigated.